We have demonstrated the decrease in suppressor T cell function in systemic lupus erythematosus, an autoimmune disease involving the production of antibodies against self. One potential theory on the pathogenesis of this disease is that autoantibodies are produced due to the lack of negative regulation of the immune system which may normally be responsible for preventing the production of autoantibodies. We have developed several lines of evidence to support this, including the existence of the defect itself and the fact that the loss of suppressor cell function is proportional to disease activity as measured by the native DNA binding. Knowledge of this proposed pathogenic mechanism raises some interesting areas of investigation towards the potential of therapeutic modification of the immune system. If we perceive autoimmunity in this regard to be due to loss of suppressor T cell function, additional such function might be provided in the form of material to stimulate T cells in general such as thymic hormones or soluble products of suppressor cells which are capable of suppressing immunoglobulin synthesis on their own. In this regard, we have demonstrated that there is a proportion of patients with SLE who respond in vivo to thymic hormones with increased suppressor cell function, and in addition, soluble products of normal peripheral blood lymphocytes which are suppressive are likewise capable of suppressing immunoglobulin production in lymphocytes from patients with systemic lupus erythematosus. This suggests that although defective in suppressor cells themselves, they are nonetheless sensitive to negative immune regulation and adoptive immunotherapy may in fact be possible. Proposed lines of investigation in the near future include further characterization of the suppressor cell defect to determine which subsets of suppressor cells are actually decreased in this disease and characterization of human soluble suppressor factors which may provide additional negative immune regulation. In addition we will further characterize potential suppressive effects of thymic hormones.